Endothelin-1 mediates hypocapnic constriction of the rabbit basilar artery in-vitro.
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Animals↗
Biomedical subjects
M Zuccarello
Publications and source records attributed to M Zuccarello.
Cervical subarachnoid hematoma of unknown origin: case report.
OBJECTIVE AND IMPORTANCE: Spontaneous spinal subarachnoid hematoma is rare, having been reported in the English literature in only seven other cases. We describe the first case of spontaneous subarachnoid hematoma located in the cervical spinal cord of a 43-year-old man. The pathologic examination showed no apparent source of bleeding, but there was evidence of cervical spondylotic myelopathy. CLINICAL PRESENTATION: The patient presented with a 10-day history of severe neck pain, followed by the onset of quadriparesis that was more evident on the left side, urinary retention, and sensory loss below C5. His medical history included hypertension. Magnetic resonance imaging showed a massive hemorrhage in the cervical spinal canal. INTERVENTION: A C4-C5 subarachnoid hematoma was removed. The patient died due to respiratory distress and uncontrollable hypotension on day 6 after surgery. Surgical exploration, neuroradiologic examinations, and autopsy showed no evidence of vascular malformations, tumors, or other possible sources of bleeding. CONCLUSION: After excluding more common causes of spontaneous subarachnoid hematoma in this patient, we suggest that chronic spinal cord compression (spondylotic myelopathy) and arterial hypertension in this patient may have caused the pathogenesis of this rare clinical entity. Experimental data supporting this hypothesis are discussed.
Adult↗
Does blockade of endothelinB1-receptor activation increase endothelinB2/endothelinA receptor-mediated constriction in the rabbit basilar artery?
The purpose of this study was to investigate whether endothelin (ET)-1 activation of ETB1 receptors influences the relative magnitude of ETA/ETB2 receptor-mediated ET-1 constriction in the rabbit basilar artery. Initial challenge of ET-1-constricted vessels with BQ610, an ETA-receptor antagonist, resulted in approximately 60% relaxation, and subsequent addition of BQ788, an ETB1/2-receptor antagonist, relaxed the remaining constriction. To test whether blockade of ETB1 receptors influenced the relative magnitude of ETA/ETB2 receptor-mediated constriction, ET-1-constricted vessels were exposed to RES-701-1, an ETB1-receptor antagonist, before challenge with BQ610 or BQ788. RES-701-1 enhanced the ET-1 constriction by approximately 60%, consistent with blockade of ETB1 receptor-mediated endothelium-dependent relaxation. In ET-1-constricted vessels treated with RES-701-1, BQ610 challenge resulted in complete relaxation, whereas BQ788 was without effect. However, when 10 nM acetylcholine was added to RES-701-1-treated ET-1-constricted vessels, (a) BQ610 challenge resulted in only approximately 30% relaxation, and subsequent BQ788 addition relaxed the remaining constriction; and (b) BQ788 challenge resulted in approximately 35% relaxation, and subsequent BQ610 addition relaxed the remaining constriction. Acetylcholine induced approximately 10% relaxation of RES-701-1-treated ET-1-constricted vessels. It is speculated that a dynamic relation exists between ETA and ETB2 receptor-mediated constriction, such that ET-1-induced ETB2 receptor-mediated constriction of the basilar artery is dependent on ETB1 receptor activation and, in the absence of this activation, the constriction reverts to completely ETA receptor mediated.
Acetylcholine↗
Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association.
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Blood Pressure↗
Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study.
BACKGROUND AND PURPOSE: The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH. METHODS: Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm(3) on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3. RESULTS: Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14; P=0.04). CONCLUSIONS: Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.
Cerebellar Diseases↗
Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection.
OBJECT: Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs. METHODS: The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0.3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post-ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry. Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2+/-1.3 to 2.8+/-0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40+/-0.10 compared with 1.26+/-0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28+/-0.05 compared with 1.46+/-0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls. CONCLUSIONS: Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.
Animals↗
Endothelin ET(B1) receptor-mediated relaxation of rabbit basilar artery.
This study tests whether endothelin receptor agonist-induced relaxation of the cerebral vasculature is mediated via endothelin ET(B1) receptor activation. Sarafotoxin S6c, an endothelin ET(B) receptor agonist, relaxed rabbit basilar artery constricted with serotonin in situ. BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH3)-Nle), and RES-701-1 (Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe-Phe-Asn-Tyr-Tyr-Trp), endothelin ET(B1/B2) and endothelin ET(B1) receptor antagonists, respectively, prevented sarafotoxin S6c-induced relaxation. RES-701-1 was selective for the ET(B1) receptor, as the endothelin-1 constriction elicited in the presence of BQ610 (homopiperidenyl-CO-Leu-D-Trp (CHO)-D-Trp-OH), an endothelin ET(A) receptor antagonist, was enhanced by RES-701-1, and relaxed by BQ788. These results represent the first demonstration of the presence of endothelin ET(B1) receptors in the cerebral vasculature.
Animals↗
Endothelin ET(B) receptor-mediated constriction in the rabbit basilar artery.
The present study tests whether endothelin ET(B) receptor activation can mediate endothelin-1 constriction in the rabbit basilar artery in situ. Endothelin-1 (30 nM) induced 27% constriction of vessels pretreated with 1 microM BQ610 (homopiperidenyl-CO-Leu-DTrp (CHO)-D-Trp-OH), an endothelin ET(A) receptor antagonist, and the resulting constriction was completely relaxed by BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH3)-Nle), an endothelin ET(B) receptor antagonist. Similarly, 30 nM endothelin-1 induced 30% constriction of vessels pretreated with 1 microM BQ788, and the resulting constriction was completely relaxed by BQ610. In contrast, sarafotoxin S6c, an endothelin ET(B) receptor agonist, did not induce constriction. This study suggests that in the basilar artery (1) endothelin ET(B) receptor activation can result in constriction and (2) the ability to elicit constriction is in some way dependent upon the agonist that activates the endothelin ET(B) receptor.
Animals↗
Endothelin B receptor antagonists attenuate subarachnoid hemorrhage-induced cerebral vasospasm.
BACKGROUND AND PURPOSE: While it has been widely reported that the vasospasm following subarachnoid hemorrhage (SAH) is prevented/reversed by endothelin (ET) receptor antagonists selective for the ET(A) receptor and by nonselective ET receptor antagonists, ie, antagonists of both the ET(A) and ET(B) receptors, there are no reports on the possible attenuation of the spasm by selective ET(B) receptor antagonists. The purpose of this study was to investigate whether (1) ET(B) receptor antagonists prevent and reverse SAH-induced spasm and (2) attenuation of the spasm results from blockade of smooth muscle ET(B) (ET(B2)) receptor-mediated constriction and/or endothelial ET(B) (ET(B1)) receptor-mediated ET-1-induced ET-1 release. METHODS: SAH-induced spasm of the rabbit basilar artery was induced with the use of a double hemorrhage model. In vivo effects of agents on the spasm were determined by angiography after their intracisternal infusion (10 microL/h) by mini osmotic pump. In situ effects of agents on the spasm were determined by direct measurement of vessel diameter after their suffusion in a cranial window. RESULTS: SAH constricted the basilar artery by 30%. Intracisternal infusion with 10 micromol/L BQ788, an ET(B1/B2) receptor antagonist, reduced the spasm to 10%. To investigate whether BQ788 prevented the spasm by blockade of ET(B1) receptor-mediated ET-1-induced ET-1 release, as opposed to ET(B2) receptor-mediated constriction, we tested whether ET(B1) receptor blockade also prevented the spasm. Indeed, intracisternal infusion with 10 micromol/L RES-701-1, a selective ET(B1) receptor antagonist, reduced the spasm to 10%. Similarly, in situ superfusion with 1 micromol/L BQ788 reversed the spasm by 40%, and 1 micromol/L RES-701-1 reversed the spasm by 50%. However, both BQ788 and RES-701-1 enhanced by 40% to 50% the 3 nmol/L ET-1-induced constriction elicited in spastic vessels previously relaxed with 0.1 mmol/L phosphoramidon, an ET-converting enzyme inhibitor. CONCLUSIONS: These results demonstrate that ET(B) receptor antagonists prevent and reverse SAH-induced cerebral vasospasm in an animal model. The likely mechanism underlying the attenuation of the spasm is blockade of ET(B1) receptor-mediated ET-1-induced ET-1 release of newly synthesized ET-1. These studies provide rationale for the therapeutic use of ET(B1) receptor antagonists to relieve the vasospasm following SAH, as well as other pathophysiological conditions involving possible ET-1-induced ET-1 release.
Animals↗
Sarcoidosis en-plaque. Report of a case and review of the literature.
A 31-year-old black male with sarcoidosis en-plaque of the dura mater, which is a rare morphological variant of neurosarcoidosis (NS), presented at our clinic. Magnetic resonance imaging (MRI) of the head with gadolinium showed non-specific enhancement of both tentorial leaves extending to the floor of right middle cranial fossa and cavernous sinus. The laboratory results were normal except for slightly increased serum angiotensin converting enzyme (SACE) (68 U/ml n = 4-56 U/ml) and cerebrospinal fluid (CSF) IgG index (0.57, n = 0.46). Biopsy of the intracranial dural lesion was consistent with sarcoidosis. Oral steroid therapy (Methylprednisolone 4 mg QID) was started and the patient became asymptomatic. However, MRI of the brain with gadolinium 2 months after biopsy showed progression and extension of the enhanced dural lesion. His SACE level was unchanged. We concluded that progression of the enhanced lesion seen in MRI could be recently formed scar tissue, new lesion or both. MRI findings should always be correlated with clinical findings for evaluation of NS during follow-up.
Adult↗
Infarction of a ventricular subependymoma after endoscopy: case report.
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Aged↗
Brain energy metabolism in the acute stage of experimental subarachnoid haemorrhage: local changes in cerebral glucose utilization.
An experimental model was used to investigate acute alterations of cerebral metabolic activity in rats subjected to subarachnoid haemorrhage (SAH). Haemorrhages were produced in anaesthetized animals by injecting 0.3 ml of autologous, arterial nonheparinized blood into the cisterna magna. Control rats received subarachnoid injections of mock-cerebrospinal fluid to study the effect of sudden raised intracranial pressure, or underwent sham operation. Three hours after SAH rats were given an intravenous injection of [14C]-2-deoxyglucose. Experiments were terminated by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied by quantitative autoradiography. In comparison with sham-operated controls, cerebral metabolic activity was diffusely decreased after SAH. Statistically significant decreases in metabolic rate were observed in 23 of 27 brain regions studied. Subarachnoid injections of mock-cerebrospinal fluid also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced and diffuse as in SAH rats. The present study shows that a widespread depression of brain metabolism occurs in the acute stage after experimental SAH and is probably secondary to the subarachnoid presence of blood itself and/or blood products.
Animals↗
Role of extracellular Ca2+ in subarachnoid hemorrhage-induced spasm of the rabbit basilar artery.
BACKGROUND AND PURPOSE: The role of extracellular Ca2+ in the maintenance of chronic vasospasm after subarachnoid hemorrhage (SAH) is largely unknown. Indeed, studies thus far have been limited to demonstrations that L-type Ca(2+)-channel antagonists were unable to reverse the spasm. This study tested whether SAH-induced vasospasm is maintained, at least in part. through the influx of extracellular Ca2+ and whether the influx of extracellular Ca2+ occurs through L-type Ca2+ channels and possibly, in addition, through store operated channels (SOCs). Furthermore, as there is considerable evidence in the literature to suggest that the spasm is mediated through endothelin-1 (ET-1) release, we tested whether the Ca2+ dependency of the spasm was consistent with the mediation of the spasm by ET-1. METHODS: Chronic spasm of the basilar artery was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1-, serotonin-, and KC1-constricted basilar artery in response to Ca(2+)-free solution, verapamil, and Ni2+ was measured in situ with the use of a cranial window. RESULTS: SAH induced 23% constriction of the basilar artery. Ca(2+)-free solution and 1 mumol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, relaxed in response to Ca(2+)-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni2+, which is known to block SOCs, induced a combined relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca(2+)-free solution, verapamil, and verapamil plus Ni2+ by 69%, 20%, and 50%, respectively (P > .05) versus respective values in SAH vessels). In contrast, control vessels challenged with 2 to 8 mumol/L serotonin, which induced a magnitude of constriction similar to those of SAH and ET-1 (22%), completely relaxed in response to Ca(2+)-free solution and verapamil. CONCLUSIONS: These results demonstrate that the maintenance of chronic spasm in the two-hemorrhage rabbit model after SAH is due to smooth muscle cell contractile mechanisms partly dependent on the influx of extracellular Ca2+. The influx of extracellular Ca2+ results from the opening of L-type Ca2+ channels and an additional channel or channels. We speculate that the L-type Ca2+ channel-independent influx of extracellular Ca2+ results from the opening of SOCs. The Ca(2+)-dependent characteristics of the spasm likely reflect the mediation of the spasm by ET-1.
Animals↗
Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by the K+ channel activator cromakalim.
BACKGROUND AND PURPOSE: Cerebral vasospasm resulting from subarachnoid hemorrhage (SAH) is refractory to most vasodilators. However, despite evidence that a mechanism underlying the vasospasm may be smooth muscle cell membrane depolarization resulting from decreased K+ conductance, the ability of K+ channel activators to relax the spasm has not been thoroughly investigated. The purpose of this study, therefore, was to investigate whether K+ channel activation selectively relaxes SAH-induced vasospasm. METHODS: Three days after SAH in the rabbit, relaxation of the basilar artery in response to the K+ channel activator cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial window. Relaxation in response to these agents was also investigated in control vessels contracted with serotonin. Membrane potential of the smooth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes. RESULTS: Cromakalim completely relaxed the SAH-induced spastic basilar artery, while staurosporine, forskolin, and sodium nitroprusside were significantly less efficacious. In contrast, sodium nitroprusside and forskolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K+ channel blocker glyburide and high [K+] prevented cromakalim-induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of serotonin-contracted control vessels. Cromakalim concentration-dependently repolarized spastic basilar artery smooth muscle cells, and the repolarization was prevented by glyburide. CONCLUSIONS: These results suggest that K+ channel activation selectively relaxes SAH-induced vasospasm. We speculate that the ability of K+ channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K+ channels after SAH.
Animals↗
The ABCs of measuring intracerebral hemorrhage volumes.
BACKGROUND AND PURPOSE: Hemorrhage volume is a powerful predictor of 30-day mortality after spontaneous intracerebral hemorrhage (ICH). We compared a bedside method of measuring CT ICH volume with measurements made by computer-assisted planimetric image analysis. METHODS: The formula ABC/2 was used, where A is the greatest hemorrhage diameter by CT, B is the diameter 90 degrees to A, and C is the approximate number of CT slices with hemorrhage multiplied by the slice thickness. RESULTS: The ICH volumes for 118 patients were evaluated in a mean of 38 seconds and correlated with planimetric measurements (R2 = 9.6). Interrater and intrarater reliability were excellent, with an intraclass correlation of .99 for both. CONCLUSIONS: We conclude that ICH volume can be accurately estimated in less than 1 minute with the simple formula ABC/2.
Blood Volume↗
Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists.
The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET) A/B receptor antagonist Ro 47-0203, 4-tert-butyl-N-[6-(hydroxy- ethoxy)-5-(2-methoxy-phenoxy)-2'-bipyrimidin-4-yl]-benzenesulfonam ide (bosentan), and the ET A receptor antagonist 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy- phenyl)-4-oxo-but-2-enoic acid monosodium salt (PD155080), in the prevention of subarachnoid hemorrhage (SAH)-induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% if control as determined by angiography. Oral bosentan and PD155080 administration after the initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155808 levels were consistent with concentrations reported to inhibit ET-1 constriction of blood vessels in vitro. These results support the use of oral administration of ET A/B and ET A receptor antagonists as potential specific treatment for vasospasm resulting from SAH in humans.
Administration, Oral↗
ORION anterior cervical plate system.
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Bone Plates↗
Immunohistochemical localization of endothelial nitric oxide synthase in vessels of the dura mater of the Sprague-Dawley rat.
Nitric oxide (NO) and the dura mater are implicated in the pathogenesis of vascular headache. Many studies have demonstrated the participation of NO in headache; however, few studies have identified NO in the dura mater. In this study, nine Sprague-Dawley rats were examined with immunohistochemistry using two different endothelial nitric oxide synthase (eNOS) monoclonal antibodies, H32 and ECNOS. eNOS was successfully localized to the endothelium of the middle meningeal artery. To the best of our knowledge, this is the first study to report NOS immunopositive endothelial cells in the blood vessels of the rat dura mater. The authors propose that NO plays an active role in dural vasodilation, contributing to the pathogenesis of vascular headache; in the future, NO inhibitors could serve as pharmacological agents to treat vascular headache.
Animals↗